The major subject of our research is chronic diarrhea, which is important for several reasons. First, the symptom is highly disabling. Second, its etiology may be hard to determine. And third, current therapies often do not bring relief. To help remedy these problems, we have established a center for the study of diarrhea and/or malabsorption syndrome. We study the physiology of absorption/secretion, the pathophysiology of diarrhea and malabsorption, and we study patients with intractable diarrhea/malabsorption. During the last 11 years we have lyophilized stool from each patient, specimens weighing kilograms are reduced to solids that can be stored in small plastic vials. When new ideas arise we can go to our stool bank and examine specimens from 100 or more patients, to test a hypothesis or to answer a question. Our research techniques includes metabolic balance methods to measure net gastrointestinal absorption or secretin of nutrients, minerals and electrolytes; or steady state intestinal perfusion which allows detailed examination of mucosal absorption or secretion rate in the jejunum, ileum and colon. Observations in patients often lead to research ideas in volunteers and vice versa. Some of our specific goals for the next five years are as follows: 1) to develop the hypothesis that inhibition of normal gastrointestinal secretions can be beneficial in the therapy of diarrhea; 2) to search for drug that inhibit active intestinal secretion of chloride, as a method for treatment of secretory diarrhea; 3) to explore the pathogenesis of idiopathic chronic diarrhea, especially in regard to ileal malabsorption of sodium chloride and bile acids; 4) to study the pathogenesis of diarrhea when it occurs as part of "Gulf War Syndrome"; 5) to evaluate the hypothesis that conjugated bile acid replacement therapy is beneficial to patients with Short Bowel Syndrome; 6) to develop more accurate methods for the measurement of caloric losses due to carbohydrate, fat and protein malabsorption; 7) to determine the physical factors which control fecal consistency; and 8) to determine the mechanisms by which gastrointestinal diseases result in disorders of acid-base balance and potassium depletion.